In the treatment of patients with certain kinds of cancer, methods are known in which radioactive particles are introduced intravascularly in order to trap the radioactive particle at a particular site for its radiation effect.
According to this technique, a small quantity of the radioactive particles are injected into the patient and a diffuse, homogeneous field of radiation within a selected region of the body is achieved by permanent lodgement of the particles in the capillary bed of the proposed area, typically the location of a tumor.
In early applications of this technique, Yttrium oxide powder was suspended in a viscous medium prior to administration. Yttrium was selected for the technique because of its suitable characteristics: it emits nearly 100 percent beta radiation. See, e.g., Nolan, et al., Intravascular Particulate Radioisotope Therapy”. The American Surgeon 35: 181-188 (1969) and Grady, et. al., Intra-Arterial Radioisotopes to Treat Cancer”, American Surgeon 26: 678-684 (1960). This method is not totally satisfactory, however. Two disadvantages of Yttrium oxide powder are its high density (5.01 gm/cm3 aka 5.01 gm/ml) and irregular particle shape. The high density of pure yttrium oxide powder makes it difficult to keep the particles in suspension in the liquids used to inject them into the body, and accelerates their tendency to settle in the blood stream prior to reaching the desired tumor. The sharp corners and edges of Yttrium oxide particles also irritate surrounding tissue in localized areas, and interfere with the uniform distribution of the radioactive particles in the tumor to be treated.
In later applications, the particles used have been microspheres composed of an ion exchange resin, or crystalline ceramic core, coated with a radioactive isotope such as P-32 or Y-90. Both ion exchange resin and crystalline ceramic microspheres offer the advantage of having a density much lower than that of yttrium oxide particles, and the ion exchange resin offers the additional advantage of being particularly easy to label. See, e.g., Zielinski and Kasprzyk, “Synthesis and Quality Control Testing of 32P labelled Ion Exchange Resin Microspheres for Radiation Therapy of Hepatic Neoplasms”, Int, J. Appl. Radiat. Isot. 34: 1343-1350 (1983). However, whenever a microsphere comprises a core material having an external surface coating which contains the radioactive isotope there is a risk that the radioactive coating may separate from the underlying microsphere core. Any mechanical breakage of the coating can release unwanted radioactivity to other parts of the human body which is highly undesirable. Further disadvantages are presented by the special handling and precautions that are necessary to coat a radioactive isotope onto a crystalline ceramic core, or to label ion exchange resin.
In still another application, microspheres have been prepared comprising a ceramic material and having a radioactive isotope incorporated into the ceramic material. While the release of radioactive isotopes from a radioactive coating into other parts of the human body may be eliminated by incorporating the radioisotopes into ceramic spheres, the latter product form is nevertheless not without its disadvantages. Processing of these ceramic microspheres is complicated because potentially volatile radioactivity must be added to ceramic melts and the microspheres must be produced and sized while radioactive, with concomitant hazards of exposure to personnel and danger of radioactive contamination of facilities.
Certain rare earth aluminosilicate glass microspheres are well known in the art as radiotherapeutics for use in humans. These have been used to irradiate diseased internal organs with beta radiation.
U.S. Pat. Nos. 4,789,501, 5,011,677, and 5,011,797 disclose that Yttrium aluminosilicate (YAS) glass microspheres have been used to treat liver cancer for many years in hundreds of patients. These microspheres lodge predominantly in the tumor vascular bed (capillary) and deliver effective, high doses of radiation.
Another rare earth aluminosilicate, Samarium aluminosilicate glass microspheres, have also been used to irradiate the organs of mammals. E. M. Erbe and D. E. Day, “Properties of Sm2O3—Al2O3—SiO2 Glasses for In vivo Applications”, J. Am. Ceram. Soc. 73(9), 1990, 2708-13.
However, there remains a need for a low density microsphere which is useful in the treatment of cancer or tumor bearing tissue, but which will not release a radioactive coating or isotope into remote parts of the body of the patient after administration, will not require any technicians to handle any radioactive materials during the formation and spheroidization of the microsphere and which have a density which will permit the microspheres to be suspended in a fluid suitable for injection into a human.